title: Developing biomarkers to predict benefit from HGF/MET pathway inhibitors.
abstract: Activation of the MET signalling pathway is critical in regulating multiple cellular processes underlying tumourigenic growth and has represented an attractive target for therapeutic intervention in cancer. Early stage clinical studies of multiple agents targeting this pathway have been undertaken, frequently in unselected patient cohorts with variable results. Promising data in patient subgroups in these studies indicate the need for predictive biomarkers to identify the patients most likely to benefit from these therapies. In this review, we discuss the current knowledge of mechanisms of MET activation, the status of the clinical evaluation of MET-targeted therapies, the associated efforts to identify and validate biomarkers, and the considerations and challenges for potential development of companion diagnostics.
authors.affiliation: Department of Research Pathology, Genentech, Inc, South San Francisco, CA, USA.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Koeppen
authors.forename: Sandra
authors.initials: S
authors.lastname: Rost
authors.forename: Robert L
authors.initials: RL
authors.lastname: Yauch
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism*; D055808:Drug Discovery; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; C066855:HGF protein, human; D047428:Protein Kinase Inhibitors; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: HGF; MET; companion diagnostic; pathway; signalling